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Bioworld:FDA grants breakthrough therapy designation to Abbisko's CSF­ 1R inhibitor, pimicotinib

Jan 30,2023
By Abbisko

The U.S. FDA granted breakthrough therapy designation to Abbisko Therapeutics Co. Ltd ('s colony-stimulating factor 1 receptor (CSF-1R) inhibitor, pimicotinib, for patients with tenosynovial giant cell tumors (TGCT) who are not able to have surgery.

Internally discovered and developed by Abbisko, of Shanghai, China, pimicotinib (ABSK-021 ( an orally bioavailable, selective, small molecule. Previous studies have shown that blocking the CSF-1R signaling pathway could modulate and change macrophage functions, and potentially treat many macrophage-dependent human diseases, chief scientific officer Zhui Chen told Bio World.

Pimicotinib is being actively investigated as a treatment for TGCT and chronic graft-vs.-host disease (cGVHD), with a number of additional indications being investigated via combination trials, he said.

The FDA breakthrough therapy designation is based on results from a phase lb clinical trial of a TGCT cohort for ABSK-021, which demonstrated significant antitumor efficacy in patients with TGCT, achieving a preliminary overall response rate of 68% and a favorable safety profile. Abbisko is conducting an on go­ ing phase lb multi-cohort expansion trial in both the U.S. and China.

"The granting of this designation also marks an essential step in the R&D and innovation of Abbisko Therapeutics in going global," said Abbisko's CEO Yao­ Chang Xu.

"Pimicotinib's U.S. breakthrough therapy designation shows FDA's recognition of pimicotinib's early data and affirmation of the company's R&D strength. It will make our clinical development process and finished drug progress more efficient, which will help shorten the time to market and benefit patients world­ wide as soon as possible," he said.

 TGCT, also known as pigmented villonodular synovitis is a locally aggressive neoplasm that affects synovial joints, mucous sacs, and tendon membranes, re­ suiting in swelling, pain, stiffness, and decreased activity of the affected joints.

The World Health Organization classifies TGCT as either localized or diffuse, with localized TGCT cases accounting for 80% to 90% of cases, and diffuse TGCT accounting for 10% to 20% of cases. Overexpression of CSF-1R occurs in most TGCTs.

Surgical resection is the standard treatment for TGCT; however, not all patients are suitable for surgical treatment as it is difficult to remove tumors in diffuse patients by surgery and could lead to severe joint damage, total synovectomy, joint replacement, or even amputation, and the risk of surgical complications can be high.

"Pretty much all the patients with diffuse-type TGCT will not be amenable to surgery," Chen said, "and for the localized-type of patients, a majority of them can undergo surgery once or twice, but after that, many of them are also not amenable to surgery."

China's National Medical Products Administration (NMPA) designated pimicotinib as a breakthrough therapy drug in July 2022. Currently, there are no highly selective CSF-1R inhibitors approved in China, and for those TGCT patients not able to have surgery, there is currently no approved drug available in China.

China's Center for Drug Evaluation within the NMPA cleared Abbisko to begin a phase Ill pimicotinib trial in TGCT. It still needs to get human genetic mate­ rial clearance as well as hospital ethics committee clearance, which typically takes a few months after the trial is cleared by the NMPA. This is standard prac­ tice for all clinical trials in China, he said.

"We're in the last few months of preparation for that phase Ill trial," Chen said, adding that Abbisko is in discussions with the FDA about the clinical trial plan for the U.S.

"Initial feedback was positive, and we're waiting for the official word from the agency about a potential phase Ill trial in the U.S." he said.

Pimicotinib is also in phase II trials in cGVHD, which is caused by donor lymphocytes attacking the recipient organs following allogeneic hematopoietic stem cell transplantation.

In cGVHD, macrophage activation that is dependent on CSF-1 promotes inflammatory responses and tissue damage, and accelerates abnormal tissue re­ pair and fibrosis, leading to the manifestations of cGVHD.

Glucocorticoids are still the standard first-line treatment for cGVHD, but more than half of treated patients will develop resistance and require second-line therapy. There are currently no approved therapeutic agents for patients with cGVHD who have failed to respond to glucocorticoid therapy in China.

 In addition to TGCT and cGVHD, Abbisko is exploring the potential of pimicotinib in treating other types of solid tumors and is collaborating with Sperogenix (Shanghai) MedTech ( in exploring its potential for treating amyotrophic lateral sclerosis among other central nervous system disorders.

Abbisko has 15 programs in its pipeline, two of which were in-licensed and the rest were internally discovered and developed, Chen said. Seven programs are now in the clinic.

In phase II trials, ABSK-091 ( is a targeted inhibitor of fibroblast growth factor recep­ tor (FGFR) subtypes 1, 2 and 3, intended as a potential treatment for multiple solid tumors, including urothelial cancer, gastric cancer, cholangiocarcinoma and lung cancer. Originally known as AZD-4547, Abbisko acquired global rights to the candidate from Astrazeneca plc in November 2019.

Homegrown ABSK-011 ( is a small-molecule inhibitor of FGFR4 in phase II trials for advanced hepatocellular carcinoma with hyper-activation of FGFl9/FGFR4 signaling.

"We are driven by internal discovery and clinical development, so all of the programs so far were initially focused on oncology, but once the programs were moved into clinical trials, because they are targets, many were associated with other non-oncology indications as well," Chen said, stressing that the company's strategy is to become a global company.

"For all of our programs, we are aiming to treat patients globally. Some programs started in the U.S. and then returned to China for late-stage trials," he said, noting that the global strategy is program-specific depending on patient availability and other factors.

Headquartered in Shanghai, the company has four different sites in China, and is running trials in the U.S., Australia and other countries. It is looking for global biopharma partners for later-stage trials.

Abbisko raised $226 million through an IPO (­ mor-treatment) in Hong Kong in October 2021, where it launched with an initial price of HK$12.46 (US$1.60) per share. Its shares (HKSE :2256) rose 1.35% on the news, closing at HK$3 per share at market close Jan. 30, 2023.

By Tamra Sarni (/authors/49-tamra-sami)

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